Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular tachyarrhythmias, heart failure and sudden cardiac death (SCD), with fibro-fatty replacement of the ventricular myocardium. Diagnosis relies upon descriptive diagnostic criteria1, and remains difficult because gene carriers manifest different phenotypes (variable expressivity) and may show no signs of disease (reduced penetrance). This recognized clinical heterogeneity2 makes the potential use of genetic diagnosis (either by linkage or mutation analysis), to determine those at risk prior to malignant clinical sequalea, extremely important. ARVC is also genetically heterogeneous, with eleven ARVC mapped loci and seven identified genes to date,3-7 several coding for desmosomal proteins (desmoplakin, plakophilin, desmoglein and plakoglobin) that are predicted to succumb to mechanical stress.5, 7 
A novel locus for ARVC (ARVD5) was mapped to chromosome 3p in 1998 as the result of a genome-wide scan in an extended family from Newfoundland, Canada with an autosomal dominant form of ARVC.8 Since then, 14 additional Newfoundland families have been identified where a disease-associated haplotype (ARVD5 haplotype) is shared with the family used to map the ARVD5 locus. This ARVD5 haplotype has been used to predict disease risk status, allowing prophylactic treatment with implantable cardioverter defibrillator (ICD) therapy that greatly improved survival.9 
Identification of the ARVD5 gene would allow improved diagnosis and therapeutic treatment of individuals with ARVD/C.